PROLIFERATING OR INTERLEUKIN-1-ACTIVATED HUMAN VASCULAR SMOOTH-MUSCLE CELLS SECRETE COPIOUS INTERLEUKIN-6
PROLIFERATING OR INTERLEUKIN-1-ACTIVATED HUMAN VASCULAR SMOOTH-MUSCLE CELLS SECRETE COPIOUS INTERLEUKIN-6
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DOI：
10.1172/jci114498
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发表时间：
1990-03-01
影响因子：
15.9
通讯作者：
LIBBY, P
中科院分区：
文献类型：
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作者：
LOPPNOW, H;LIBBY, P
构成血管壁的细胞似乎积极参与局部免疫和炎症反应，以及某些血管疾病。我们在这里测试了平滑肌细胞（SMC）是否能产生重要的炎症介质IL6。体外未刺激SMC细化5倍。103 pg recIL6/24h(即生物活性相当于5倍。103 pg重组IL6 (recIL6)，用B9-assay（用recIL6标准物）测定。一些病理生理相关因素增加了SMC中il - 6的释放，包括10 .mu。g LPS/ml (104 pg recIL6)， 10 ng肿瘤坏死因子/ml（4倍）。104 pg recIL6)，最显著的是10 ng IL1/ml (.gtoreq。3.2的同学们。105 pg recIL6)。IL6活性的产生与IL6 mRNA的积累和新生合成相对应。SMC迅速释放新合成的IL6，因为很少有代谢标记的物质保持细胞相关。在il - 1刺激的SMC上清液中，il - 6占分泌蛋白的4%。在正常血管中，SMC很少分裂，但SMC增生可发生在高血压或动脉粥样硬化过程中。因此，我们在体外测试了il - 6的产生与血小板衍生生长因子（PDGF）的SMC增殖之间的关系。静止SMC释放少量il - 6活性，而PDGF （1-100 ng/ml）产生浓度依赖性和协调增强SMC增殖和il - 6释放（生长与il - 6释放的线性回归结果为0.0.9）。IL6本身既不刺激也不抑制SMC的生长或IL6的产生。在短期类器官培养中研究的完整内侧条产生了大量的IL6，与培养SMC的结果相似。这些发现说明了血管SMC的一种新功能，这些细胞可能参与局部免疫调节、各种重要血管疾病的发病机制以及炎症反应。
The cells that make up blood vessel walls appear to participate actively in local immune and inflammatory responses, as well as in certain vascular diseases. We tested here whether smooth muscle cells (SMC) can produce the important inflammatory mediator IL6. Unstimulated SMC in vitro elaborated 5 .times. 103 pg recIL6/24h (i.e., biological activity equivalent to 5 .times. 103 pg recombinant IL6 (recIL6), as determined in B9-assay with a recIL6 standard). Several pathophysiologically relevant factors augmented IL6 release from SMC including 10 .mu.g LPS/ml (104 pg recIL6), 10 ng tumor necrosis factor/ml (4 .times. 104 pg recIL6), and most notably 10 ng IL1/ml (.gtoreq. 3.2 .times. 105 pg recIL6). Production of IL6 activity corresponded to IL6 mRNA accumulation and de novo synthesis. SMC released newly synthesized IL6 rapidly, as little metabolically labeled material remained cell-associated. In supernatants of IL1-stimulated SMC, IL6 accounted for as much as 4% of the secreted proteins. In normal vessels SMC seldom divide, but SMC proliferation can occur in hypertension or during atherogenesis. We therefore tested the relationship between IL6 production and SMC proliferation in response to platelet-derived growth factor (PDGF) in vitro. Quiescent SMC released scant IL6 activity, whereas PDGF (1-100 ng/ml) produced concentration-dependent and coordinate enhancement of SMC proliferation and IL6 release (linear regression of growth vs. IL6 release yielded r > 0.9). IL6 itself neither stimulated nor inhibited SMC growth or IL6 production. Intact medial strips studied in short-term organoid culture produced large quantities of IL6, similar to the results obtained with cultured SMC. These findings illustrate a new function of vascular SMC by which these cells might participate in local immunoregulation and in the pathogenesis of various important vascular diseases as well as in inflammatory responses generally.